The overall objective of this project is to provide a better understanding of the mechanism of insulin resistance in muscle in three models of hyperinsulinemia and/or obesity in the rat and to determine the effects of acute exercise and physical training on this phenomenon. Studies will be conducted in normal laboratory rats as they become older and more obese, in rats made insulin resistant by chronic administration of insulin and in genetically obese Zucker rats (fa/fa). Using an in vitro incubation system for studying rat soleus muscle, the specific mechanism of decreased insulin action on muscle in the above animals will be investigated by examining the binding of radioactively labelled insulin to specific receptors in muscle, determining the effect of insulin on glucose transport and phosphorylation as measured by uptake of radioactively labelled 2-deoxyglucose, determining glucose metabolism by measuring D(5-3H) glucose incorporation into glycogen and 3H2O and determining whether or not the glucose fatty acid cycle is operative in insulin resistant muscle by measuring intracellular concentrations of citrate, glucose-6-phosphate and glycogen. The effect of physical conditioning and acute exercise on the development of insulin resistance in muscle and the reversal of insulin resistance once it has become established will be studied in these animal models. Effects of exercise will be compared to effects of dietary restriction in both acute and chronic experiments.